3374
J. Am. Chem. SOC.1985,107, 3374-3375 Scheme I
p
-I+
& I L
-1
/ 12-
e I
L2ReH2
L
3 -
2 -
LiAlH (LiAIDj
K2CO3
Me RLi
I L2ReH2
6 -
Figure 2. Schematic representation of the lipid aggregates formed with N+CSAla2C14(0-C) and (SO3-)C5A1a2Cl4 (0-C) mixed a t the equimolar ratio in water.
aggregates, in which an effective hydrogen-bonding interaction among head groups is presumably the predominant factor controlling the stabilization of such aggregates. In conclusion, an attractive interaction among polar head groups of lipid molecules in aggregates is the primarily important factor for the formation of globular aggregates, and the subsequent hydrophobic interaction among these aggregates results in the closely packed arrangement. In addition, the hydrogen-belt domain in such aggregates may also be responsible for the morphological stabilization. Registry No. N+CSAla2CI4,83825-02-9; (SO3-)CSAla2Ci4, 9536272-4. (6) Murakami, Y.; Nakano, A.; Kikuchi, J.; Takaki, T.; Uchimura, K. Chem. Lett. 1983, 1891-1894.
Regioselective Nucleophilic C-Alkylation of the Pyrrole Ring in an (7pPyrrolyl)iodohydridorheniumComplex Hugh Felkin* and Janusz Zakrzewski Institut de Chimie des Substances Naturelles C.N.R.S.,91 190 Gij-sur- Yvette, France Received December 21, 1984 The electrophilic C-alkylation of pyrrole (as its magnesium salt) shows only modest selectivity for 2-~ubstitution,’*~ and C-alkylated pyrroles are generally prepared by less direct routes, including cyclization of acyclic precursors.’ Here we report the preparation of an 7-pyrrolyl iodo hydrido complex of rhenium 4 which undergoes nucIeophilic C-alkylation in high yield (>90%) at the C-2 position of the pyrrolyl ligand. Whereas the activation toward nucleophiles of weakly nucleophilic organic molecules such as arenes by coordination to transition-metal centers offers one of the most useful synthetic strategies involving organotransitionmetal comple~es,~ this kind of “Umpolung” does not seem to have been achieved previously in the case of the more nucleophilic (1) Sundberg, R. J. In “Comprehensive Heterocyclic Chemistry”; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford, 1984; Vol. 4, Chapter 3.06. (2) (a) Skell, P. S.; Bean, G. P. J. Am. Chem. SOC.1962,84,4655-4660. (b) Wang, N. C.; Teo, K. E.; Anderson, H. J. Can. J. Chem. 1977, 55, 4 112-4 116. (3) Davies, S. G. “Organotransition Metal Chemistry: Applications to Organic Synthesis”;Pergamon Press: Oxford, 1982; Chapter 4. Collman, J. P.; Hegedus, L. S. “Principles and Applications of Organotransition Metal Chemistry”; University Science Books: Mill Valley, CA, 1980; Chapter 14. Semmelhack, M. F.; Garcia, J. L.; Cortes, D.; Farina, D.; Hong, R; Carpenter, B. K. Organometallics 1983, 2, 467-469 and references therein.
WH(”’
I L2ReH2 ~
-9
8a -a,
R=Me
b,
R = n-Bu
c,
R
= t-Bu
aromatic nitrogen heterocycle^.^ Our results are summarized in Scheme I (L = PPh,). The v-pyrrolyl dihydrido complex 25 was obtained in 61% yield by refluxing bis(tripheny1phosphine)rhenium heptahydride (1)6with pyrrole (10 equiv) and 3,3-dimethylbutene (10 equiv) in T H F ( 5 mi^^).^ Like pyrrole itself, this neutral complex reacts with ~
(4) Pannell, K. H.; Kalsotra, B. L.; Pirkinyi, C. J. Heterocycl. Chem. 1978, 15, 1057-1081. Bogdanov, G. M.; Bundel, Yu. G. Khim. Geterosikf. Soedin. 1983,8, 1155-1 172. Nucleophilic addition to (+ndole)Cr(CO), has been investigated; in this case, however, the Cr(C0)3 unit is coordinated to the carbocyclic ring and addition takes place on this ring: Semmelhack, M. F.; Wulff, W.; Garcia, J. L. J. Orgunomet. Chem. 1982, 240, C5-ClO. Very recently, nucleophilic addition to a thiophene manganese cation has been reported: Lesch, D. A.; Richardson, J. W., Jr.; Jacobson, R. A.; Angelici, R. J. J. Am. Chem. SOC.1984,106, 2901-2906. (5) All the organometallic complexes described are yellow (or orange, 4) air-stable crystalline solids; they gave satisfactory elemental analyses (C, H, N, P) (except for the deuterio analogues, which were not analyzed). Selected NMR data: 2 ‘H (80 MHz, CD2C12)6 5.43 (s, H2, H5), 4.53 (s, H3, H4), -10.07 (t, J = 41 Hz, ReH,); 31P{ArH} (162 MHz, CD2C1,) 6 33.61 (downfield from external H3P04)(t, J = 41 Hz). 3 ‘H (80 MHz, acetone-d,) 6 6.51 (s, H2, H5), 5.45 (s, H3, H4), 2.71 (s, Me), -8.00 (t, J = 41 Hz, ReH,). 4 ‘H(80 MHz, CD,Cl,) 6 5.64 (s, H2, H5), 4.49 (s, H3, H4), -10.23 (t, J = 48 Hz, ReH). 5a ‘H (200 MHz, C6D6) 6 5.47 (s, H5), 4.49 (d, J = 2 Hz) and 4.21 (d, J = 2 Hz) (H3, H4), 2.23 (s, Me), -9.52 (t, J = 40 Hz, ReH,). 5b ‘H (200 MHz, C6D6)6 5.51 (s, H5), 4.58 (d, J = 2 Hz) and 4.22 (d, J = 2 Hz) (H3, H4), 2.52, 1.51, 1.23 (m, (CHJ3), 0.79 (t, J = 8 Hz, CH3), -9.49 (t, J = 40 HZ, ReH2). SC ‘H (80 MHz, C6D6) 6 5.38 (s, H5) 4.67 (d, J = 2 Hz) and 3.80 (d, J = 2 Hz) (H3, H4), 1.13 (s, t-Bu), -9.28 ( 2 , J = 40 Hz, ReH2). 6-H ‘H (200 MHz, acetone-d,) 6 5.22 (dt, J = 3.6, 5.4 Hz, H5-exo), 5.04 (s, H2), 3.66 (d, J = 3.6 Hz,HS-endo), 3.30 (d, J = 3.6 Hz) and 1.50 (d, J = 3.6 Hz)(H3, H4), 1.33 (s, Me), -2.0 (br) and -10.8 (br) (ReH2). 8a ‘H (200 MHz, C6D6)6 4.28 (s, H3, H4), 2.23 (s, Me), -9.43 (t, J = 40 Hz, ReH,). (6) Chatt, J.; Coffey, R. S. J. Chem. SOC.A 1969, 1963-1972. Baudry, D.; Ephritikhine, M.; Felkin, H. J. Orgunomet. Chem. 1982, 224, 363-376. (7) For other reactions involving this L2ReH7 olefin system, see: Baudry, D.; Daran, J. C.; Dromzee, Y.; Ephritikhine, M.; Felkin, H.; Jeannin, Y.; Zakrzewski, J. J. Chem. SOC.,Chem. Commun. 1983, 813-814 (furan). Baudry, D.; Ephritikhine, M.; Felkin, H.; Jeannin, Y.; Robert, F., J. Orgunomet. Chem. 1981,220, C7-ClO (benzene). Baudry, D.; Ephritikhine, M.; Felkin, H.; Zakrzewski, J. Tetrahedron Lett. 1984,25, 1283-1286 (n-alkanes). Baudry, D.; Ephritikhine, M.; Felkin, H.; Holmes-Smith, R. J . Chem. SOC., Chem. Commun. 1983, 788-789 (cycloalkanes).
0002-7863/85/ 1507-3374$01.50/0 63 1985 American Chemical Society
+
J . Am. Chem. SOL 1985, 107, 3375-3377 electrophiles, and it was converted (CF3S03Mein CH2C12,20 "C; 88% yield) into the q-1-methylpyrrole dihydrido cation 3, in the hope that the positive charge would promote nucleophilic attack, as occurs with cationic arene c ~ m p l e x e s . ~ This first approach to the nucleophilic alkylation of pyrrole proved disappointing. Although the dihydrido cation 3 reacted smoothly (THF, 0 "C) with LiAIH, and LiAlD, to give (93% yield) the neutral dihydrido complexes 6-H and 6-D* [which were converted into 1-methylpyrrole (9-H) and 1-methyl- [2-*H]pyrrole (9-D)9 by heating in CsD5N (90 "C, 10 min)], only intractable mixtures were obtained with lithium alkyls or dimethyl sodiomalonate. We have discovered, however, that lithium alkyls readily alkylate the neutral q-pyrrolyl iodo hydrido complex 4, obtained in 80% yield by treatment of 2 with I, (1 equiv) and K2C03 (excess) (CH2C12,20 "C). Thus, 5a was formed immediately and essentially quantitatively (92% isolated yield) when a solution of MeLi (1.2,equiv) was added to 4 (in THF, 0 "C); similarly, n-BuLi gave 5b (90%), and t-BuLi (at -80 "C) gave 5c (97%). The 7-2-alkylpyrrolyl complexes 5a-c could be converted into the free 2-alkylpyrroles 7a-cI0 (5a and 5b by heating at 90 "C in Me,SO-d, containing HBF.,, and 5c by vacuum pyrolysis at 150-180 "C). The procedure could be repeated; the ~p2-methylpyrrolylcomplex 5a, when treated successively with 12-K2C03 and MeLi, without isolating the intermediate iodo hydrido complex, gave the 7-2,5-dimethylpyrrolyl complex 8a (94% isolated yield). A special effort was made in this case to determine the regioselectivity of the reaction; no trace of the 2,3- or 2,4-dimethylpyrrolyl isomers could be detected in the crude, unrecrystallized q-2,S-dimethylpyrrolyl complex 8a by 200-MHz ' H NMR, indicating that the reaction is >98% regioselective. LiAlH, and LiAlD, also reacted with the iodo hydrido complex 4, but much more slowly (THF, 20 "C, 2 h), to give 5 (R = H) ( ~ 2 and ) its 2-deuterio analogue 5 (R = D) (79% yield)." This remarkably facile alkylation (4 5), in which nucleophilic attack on a coordinated aromatic moiety is accompanied by migration of hydrogen from carbon to metal and elimination of a good leaving group (halide) from the metal, appears to have some precedent in cyclopentadienyl transition-metal systems.I2 The presence of a leaving group is essential; the dihydrido complex 2 is not alkylated by lithium alkyls under the same conditions. We imagine that the reaction is either an entirely concerted nucleophilic process or, more probably, that it is initiated by a single electron transfer, followed by loss of iodide from the 19e radical anion of 4.
-
Note Added in Proof. Since this communication was submitted, we have found that aromatic lithium reagents also react with the iodo hydrido complexes under the same conditions (0 "C), and with the same high regioselectivity and yield, as the aliphatic lithium reagents described above. Thus, 5 (R = Ph) and 5 (R = 5-methyl-2-furyl) were obtained from 4 in >85% yield. 8 (R
(8) (a) The ' H NMR and IR spectra of 6-H and 6-Dindicate that hydride attacks the I-methylpyrrole ring in 3 from the uncomplexed, exo side. The splitting pattern of the NMR signal of the introduced hydrogen (6 5.22, absent in the spectrum of 6-D) can be explained by long-range coupling with the two "P nuclei, characteristic for H-exo.8b Furthermore the medium-intensity band at 2820 cm-l (u(C-H) exo) in the IR spectrum of 6-H is absent in the spectrum of 6-D, in which u(C-D) exo is observed at 2030 cm-I. (b) Davies, S . G.; Moon, S . D.; Simpson, S. J.; Thomas, S. E. J . Chem. SOC.,Dalton Trans. 1983, 1805-1 806. (9) 9-H was identified, without isolation, by comparison of its 'H NMR spectrum with that of a commercial sample; integration of its 'H NMR signals showed that 9-D was deuteriated exclusively on C-2. (IO) 79 and 7b were identified, without isolation, by their 'H NMR spectra.& 7c was isolated in 84% yield: IH NMR (200 MHz, CDCI,) 6 8.04 (br, NH) 6.69 (m,H5), 6.12 (m)and 5.94 (m)(H3, H4), 1.25 (s, t-Bu). (11) Integration of its ' H NMR signals showed that 5 (R = D) was deuteriated exclusively on C-2. (12) Green, M. L. H.; Lindsell, W. E. J . Chem. SOC.A 1969, 2215-2218. Dias, A. R.; Romao, C. C. J . Organomet. Chem. 1982, 233, 223-231. See also: Reger, D. L.; Belmore, K. A.; Atwood, J. L.; Hunter, W. E. J . Am. Chem. SOC.1983, 105, 5710-5711. (We thank a referee for drawing our attention to this work.)
0002-7863/85/1507-3375$01.50/0
3375
= Ph) was obtained from 5 (R = Ph) in 87% yield without isolating the iodo hydrido intermediate and afforded pure 2,5diphenylpyrrole (92%, no isomers detectable by NMR) upon treatment with Me2SO-HBF,.
Design of Stereoselective Etchants for Organic Crystals. Application for the Sorting of Enantiomorphs and Direct Assignment of Absolute Configuration of Chiral Molecules L. J. W. Shimon, M. Lahav,* and L. Leiserowitz* Department of Structural Chemistry The Weizmann Institute of Science Rehovot, Israel 76100 Received August 27, I984 Despite the widespread use of etching in the material sciences,'-3 the selection of appropriate etchants is generally done with a combination of "inspiration and intuition".' Recently we reported changes in crystal habit induced during crystallization by the presence of minute amounts of additives with structures similar to that of the ~ u b s t r a t e . ~A correlation was established between the molecular structure of the additive, the crystal structure of the substrate, and the affected growth directions. We found that the additive may bind stereoselectively to the affected crystal face, as if it were a substrate molecule, on the condition that its modified moiety emerges from the crystal surface. During the crystal's growth this adsorption hinders growth by disturbing deposition of oncoming layers on that face. During dissolution such additive molecules should adsorb in an analogous stereoselective manner only at those faces whose molecules are so oriented as to receive this additive. We report that a growth inhibitor of a particular face can act as an etchant of that same face during partial dissolution. The two examples covered here deal with etching by chiral additives of a mixture of enantiomorphous crystals of (R,S)-asparagine which, as a conglomerate, resolves spontaneously on crystallization and with the etching by chiral additives of the enantiotopic faces of the centrosymmetric crystal of glycine. Growth experiments have shown that only R amino acid additives may bind to the surfaces of (R)-asparagine crystals, while the S additives may bind only to the (S)-asparagine crystals.4a The additive aspartic acid may bind only to those crystal faces of asparagine which allow its modified moiety, the hydroxyl oxygen, to emerge from the crystal surface, Le., the (OlOl face (Figure la). A loss of energy due to replacement of the N-H.a-0(carboxylate) hydrogen bond between asparagine molecules by an 0. .Orepulsion between the hydroxyl oxygen of the P-carboxy group of aspartic acid and the carboxylate oxygen of asparagine inhibits the aspartic acid's adsorption when it approaches an (010) face in the reverse manner.5 The conditions necessary for binding are met in two out of the four symmetry-related sites at the (010) faces of this orthorhombic P2,2,2, crystal.6 When crystalline (R,S)-asparagine-H,O is partially dissolved in a solution containing 20% (R)-aspartic acid, etch pits are formed only on the (010) faces7 of the R crystals (Figure lb); the S crystals remain
-
(1) Thomas, J. M. Ado. Catal. 1969, 19, 337. Thomas, J . M.; Evans, E. L.; Clarke, T.A. J . Chem. SOC.A 1971, 2338. (2) Honess, A. P. "The Nature, Origin and Interpretation of Etch Figures on Crystals", Wiley: New York, 1927; p 6. (3) Johnston, W. G. Prog. Ceram. Sci. 1963, 3, 42. (4) (a) Addadi, L.; Berkovitch-Yellin, Z . ; Domb, N.; Gati, E.; Lahav, M.; Leiserowitz, L. Nature (London) 1982, 296, 21. (b) Berkovitch-Yellin, Z . ; Addadi, L.; Idelson, M.; Leiserowitz, L.; Lahav, M. Nature (London) 1982, 296, 27. ( 5 ) Verbist, J. J.; Lehman, M. S.; Koetzle, T. F.; Hamilton, W . C. Acta Crystallop., Sect. B 1972, B28, 3006. (6) Berkovitch-Yellin, Z.; Addadi, L.; van Mil, J.; Lahav, M.; Leiserowitz, L., unpublished results. (7) The crystals of asparagine were partially dissolved in a solution containing 50 mg of (R,S)-asparagine and I O mg of (R)-aspartic acid per 1 mL of H20at 25 OC for 5 min. The etching was seen on the (010) faces under both optical and scanning electron microscopes.
0 1985 American Chemical Society
